An effective vaccine is the only practical way to halt the AIDS epidemic. The greatest challenge in developing an effective HIV vaccine is antigenic variation. Therefore, the present project aim is to enhance the understanding of antigenic variation by characterizing intra-subtype sequence variation among gpl20 genes from incident (new) infections, and identifying novel antigens that will be manufactured and advanced into clinical trails. Samples will be collected from VaxGen's current Phase III U.S. AIDS vaccine clinical trials. Amino acid sequences will be analyzed using new software that maps sequence variation onto the 3D crystal structure of gp120 to define substitutions that may alter the antigenic profile. This study will provide a database of virus sequences currently circulating throughout North America, with reference to approximate time of infection, geographic distribution, and the nature of source material. These data will aid in incorporating new antigens to improve current HIV vaccine efficacy against variants of subtype B by guiding selection of the most appropriate envelope antigens for next generation HIV vaccines.